As we enter 2025, we’re excited to keep growing our partnership with the wonderful Wolfram syndrome community—researchers, scientists, patients, and families. This year is brimming with new opportunities to engage, evolve, and amplify our impact together. Let’s celebrate a remarkable year ahead, working hand in hand to create meaningful change. Thank you for being such an invaluable part of our community. Always remember, there is HOPE!
2024 was a noteworthy year for WS research, but we have much to achieve in 2025. We greatly appreciate our donors’ steadfast support, accelerating research to improve the lives of those with Wolfram syndrome. A breakthrough is near, but we need your help! Together, we can accomplish great things. We invite you to donate today and join our journey toward a better future.
Chief Medical and Scientific Officer for the Snow Foundation
The accomplishments of the Wolfram syndrome research community over the past decade or so have been remarkable, and recently, that progress seems to have accelerated. The WS Research Conference in Windsor, England, in October was a tremendous success; 32 WS researchers gathered in one room, presented data, discussed their findings, and determined the next steps for their research. This collaboration inspired new ventures, including the creation of international consensus guidelines for the diagnosis and treatment of WS, new plans to evaluate small molecules for the treatment of WS, renewed efforts in the realms of gene editing and gene therapy for WS, and so much more. The Snow Foundation is delighted and honored to support these research endeavors (please see descriptions of these projects below).
As clinicians worldwide recognize and diagnose WS more quickly, The Snow Foundation is assisting many more individuals with a new diagnosis of WS and WFS1-related disorder. We are honored to support these newcomers to the WS community; we hope to provide them not only with day-to-day aid and encouragement, but also with the hope of new treatments for WS on the horizon.
Below, you will read about current projects supported by The Snow Foundation that aim to
• Slow Progression of WS (AMX0035, small molecules/approved compounds)
• Stop the Progression of WS (gene therapy and gene editing)
• Replace Damaged cells in WS (MANF peptide)
Additional projects listed below will help us better understand the effect of WS on cells and on the body as a whole and how we may help to ameliorate symptoms more effectively than ever before.
We have traveled a long distance toward treating and curing WS during the past decade. We are excited to watch 2025 unfold as our marathon becomes a sprint toward the finish line!
The Amylyx HELIOS trial is a 12-participant, single-site, open-label, Phase 2 clinical trial designed to evaluate the safety and tolerability of AMX0035, an investigational medicine, and various measures of endocrinologic, neurologic, and ophthalmologic function in adult participants living with Wolfram syndrome. In October 2024, Amylyx announced positive topline results from HELIOS (NCT05676034). The primary endpoint of HELIOS is measuring C-peptide response, which is a measure of the ability of the pancreas to produce insulin. After 24 weeks of treatment with AMX0035, improvement in C-peptide response was observed, which means that pancreatic function improved. AMX0035 was generally well-tolerated. All adverse events (AEs) were mild or moderate, and no serious AEs were related to AMX0035 treatment.
HELIOS is no longer enrolling participants but remains ongoing for those already enrolled. Limitations of HELIOS include that it is a small study and there is no placebo group to compare the AMX0035 group to. Thus, AMX0035 will need to be studied further in Wolfram syndrome in a Phase 3 program. Amylyx continues to engage with FDA and other stakeholders to inform a Phase 3 program and expects to provide an update in 2025.
Living with Wolfram Syndrome: Sharing Raquel’s Story Raquel and her mother, Stephane Gebel, recently had the opportunity to share Raquel’s story about living with Wolfram syndrome, how it’s impacted Raquel’s childhood and college experience, and what we’d like those who are researching Wolfram syndrome to know in order to make a meaningful difference for our community. Check out the resulting video here to hear their perspectives:https://www.amylyx.com/wolfram-syndrome
Université de Montpellier (France) – Researchers are determining the efficacy of gene therapy for preserving vision and hearing in WS and testing novel therapeutics to prevent the degeneration of retinal ganglion cells in WS.
KU Leuven (Belgium) – Researchers at KU Leuven are continuing their work investigating gene editing (base pair editing) for use as a therapy to preserve vision in Wolfram syndrome.
The National Research Council Institute of Neuroscience (Milan) – With meticulously developed vectors, retinal cell-specific WFS1 gene therapy is being administered to treat blindness in Wolfram syndrome mice. The Snow Foundation is excited to collaborate with Be A Tiger Foundation to make this happen.
San Raffaele Scientific Institute (Italy) – This project will evaluate the use of gene therapy as a treatment for WS, and evaluate the role that inflammation plays in WS. They plan to deliver functioning, wild-type WFS1 protein to WS mutant precursor white blood cells. This delivery will occur in a mouse model with humanized beta (insulin producing) cells. In doing so they hope to decrease inflammation in WS, and also further refine a method of delivering wild-type WFS1 to WS mutant cells through gene therapy.
University of Tartu (Estonia) – Investigations have been completed determining the effects of liraglutide, Gaba, and taurine in WS cells and mice. TSF plans to continue partnering with Estonian researchers to expand the search for repurposed therapeutics and small molecules supporting cell function in WS.
Washington University School of Medicine (USA) – MANF preclinical data collection is ongoing by Dr. Fumihiko Urano, who is using MANF as a peptide to support retinal cell regeneration. TSF is currently focused on facilitating the development of MANF as a WS therapeutic. We aim to help get MANF from the lab to clinical trial for WS. We are also evaluating the safety and effectiveness of combination therapy with Amylyx, alongside Liraglutide or Mounjaro.
I hope everyone is keeping OK and escaping the winter bugs that are going around.
I would like to give a short update on our next steps now that the TREATWOLFRAM trial has finished. The last participant finished the trial during November 2024. We are currently collecting all the outstanding data from study sites (in France, Poland, Spain, and UK). We hope to complete this by end February or beginning of March. The Clinical Trials Unit will then ‘lock’ the database so that our statistician Tori Homer can start the analysis of all the data. We have so much data, on most aspects of Wolfram, that it may take 6-8 weeks to complete the analysis. Tori will then send me a Clinical Study Report. I hope this will be ready by May, in time to present the results to everyone at the Wolfram International meeting in Paris in June.
If the TREATWOLFRAM trial shows that sodium valproate is safe and effective in slowing disease progression in Wolfram, then we will be able to prescribe it ‘off licence’ to patients in the UK. We will strictly follow the national patient safety alert advice so that it is not given to females while they are trying to conceive or while they are pregnant. We will work with medicines regulators in UK, USA and Europe (MHRA, FDA, EMA) to apply for valproate to be licensed as a treatment for Wolfram.
If the TREATWOLFRAM trial does not show that sodium valproate is safe and effective, then we will use the fantastic quality natural history data on our large international cohort of patients, to support the design of new clinical trials that are shorter and more efficient and get results quicker. This means that we should be able to proceed to new clinical trials quickly.
All our study team owes a big thank you as always to Wolfram syndrome UK, Snow Foundation, Eye Hope Foundation, and French Wolfram Association for their generous support, and for bringing the Wolfram community of families, researchers and health care professionals together.
With Rare Disease Day approaching, I want to take a moment to recognize the incredible strength of the Wolfram syndrome community. The increasing number of patients referred to us highlights the urgency of our work in developing effective treatments. Every day, I receive messages from patients and families looking for updates, which reinforces the importance of our research. This day is an opportunity to raise awareness, push for progress, and reaffirm our dedication to improving care and finding better treatments. I am pleased to share the latest updates with you.
Ongoing Clinical Trial of AMX0035 in patients with Wolfram Syndrome
https://clinicaltrials.gov/study/NCT05676034
We continue working with Amylyx Pharmaceuticals to evaluate AMX0035, an encouraging oral medication aimed at slowing the progression of Wolfram syndrome. The Phase 2 clinical trial began in April 2023, with interim results announced in April and October 2024. The latest analysis in October included assessments at Week 48 and continued to show encouraging outcomes. Among the eight participants evaluated, sustained improvements were observed in pancreatic beta cell function, blood sugar control, and neurological symptoms. C-peptide levels, a marker of pancreatic beta cell function, remained stable or improved in most participants, which contrasts with the typical decline seen in Wolfram syndrome. Encouragingly, measures of vision function also showed stabilization or modest improvement in several individuals. Importantly, AMX0035 continued to be well tolerated, with no new safety concerns reported. These findings reinforce the potential of AMX0035 as a disease-modifying therapy for Wolfram syndrome. Ongoing discussions with Amylyx and the U.S. FDA will determine the next steps toward further development and potential regulatory pathways.
For more details, please visit: https://www.amylyx.com/news/amylyx-pharmaceuticals-announces-positive-topline-results-from-phase-2-helios-clinical-trial-demonstrating-sustained-improvements-with-amx0035-in-people-living-with-wolfram-syndrome
Gene-Editing Therapy
We are making steady progress in developing gene-editing therapies to target the underlying cause of Wolfram syndrome. Our focus is on second- and third-generation gene-editing technologies: base editing and prime editing. These methods offer precise correction of genetic variants with increasing efficiency and safety. To enhance effectiveness, we are testing base editing with engineered DNA-free virus-like particles (eVLPs) and dual adeno-associated virus (AAV) systems. Our research uses brain cells differentiated from patient iPSCs and rodent models carrying WFS1 variants. One of the new variants being studied is WFS1 c.1672C>T (p.Arg558Cys) associated with a mild form of Wolfram syndrome commonly seen in the Ashkenazi-Jewish population. Our goal is to develop a gene-editing therapy that could be available within five to ten years.
Regenerative Therapy for Optic Nerve Atrophy
As most of you know, vision loss from optic nerve atrophy is a major challenge in Wolfram syndrome. We are developing regenerative therapies, especially the use of a neurotrophic factor called MANF. MANF has protective effects against ER stress, a key driver of Wolfram syndrome, and helps support stressed nerve cells. Pre-clinical studies, including experiments with humanized mouse models of Wolfram syndrome, show encouraging results. We are currently refining methods to deliver MANF effectively to the eye. To accelerate this work, we are collaborating with patient organizations to gather input and drive the development of this therapy. By working closely with these organizations, we aim to incorporate patient perspectives into our research and clinical trial design. This collaborative approach strengthens our commitment to making regenerative therapy a viable option for individuals with Wolfram syndrome. We aim to begin clinical trials for this therapy within the next five to seven years.
Wolfram Syndrome and Related Disorders Clinic
To enhance care for patients with Wolfram syndrome and WFS1-related disorders, we operate the multi-disciplinary Wolfram Clinic at Washington University Medical Center. This clinic delivers expert care to patients from across the United States and worldwide. I am grateful to the Snow Foundation, the Ellie White Foundation, Unravel Wolfram Syndrome, and the various Wolfram syndrome support groups for their support in connecting patients with our clinic. We offer comprehensive services, including genetic evaluations, counseling, and personalized management plans developed in collaboration with specialists across multiple disciplines. We warmly welcome both international and out-of-state patients.
For more information, please visit our website:
Introducing a Nurse Navigator for Wolfram Syndrome
I am pleased to introduce Ashley Raterman, RN, as our new nurse navigator for the Wolfram syndrome clinic and research programs. She will coordinate our multidisciplinary clinic at Washington University Medical Center, oversee the International Registry for Wolfram Syndrome, and work closely with patient organizations. For any questions, she can be reached at 314-477-1527 or via email at wolframsyndrome@wustl.edu.
Thank you for your ongoing support. We remain committed to advancing research and improving care for those affected by Wolfram syndrome.
Sincerely,
Fumi
Fumihiko (Fumi) URANO, MD, PhD
Samuel E. Schechter Professor of Medicine
Washington University School of Medicine
The 9th Annual Global Research Symposium: In collaboration with WSUK, the 9th Annual Wolfram Syndrome Research Symposium was held in Windsor, England, this past October. Over 30 international WS researchers and scientists attended for two days of remarkable presentations, extensive collaborations, and discussions about the next best steps for WS research and treatment development. We welcomed new attendees from Slovakia, Brazil, and Italy. Notes from the presentations have been shared with all WS researchers and the global community and can also be found via the link in the article below on the WSUK websiteand theWSRA website.
The Snow Foundation is excited to announce that a global Core Group of WS Clinicians and Foundations is developing comprehensive guidelines for diagnosing and treating Wolfram syndrome. This document aims to provide clear guidance on the criteria and decision-making processes related to the diagnosis, management, and treatment of Wolfram syndrome across various areas of healthcare.
German, Italian, and Brazilian Portuguese versions are coming soon
We have partnered with the National Organization of Rare Disorders, Inc., “NORD,” to implement the first-ever WS global patient-owned registry, a priority in the field of rare disease. Please help us improve patient care, strengthen our voice, and improve the chance for quicker drug development. Support The Snow Foundation’s vision of “a world without Wolfram syndrome.” Sign up today at wsglobalregistry.iamrare.org to contribute information about your WS experience and to be eligible to receive critical information about treatment, research, resources, and other initiatives. If you have any questions, please email Pat Gibilisco at pat@thesnowfoundation.org.
Join our Wolfram syndrome community, which offers support and companionship. This private Facebook site serves as a place to receive guidance and suggestions, such as the best questions to ask physicians, how to address symptoms that other families may have experienced, or you may join anonymously and learn from other families with older children who have had this diagnosis. These families get what it’s like to live in the rare disease lane and will help you navigate this journey.
2024 FAMILY Fundraisers
Thank You!
Thank you to families and businesses for your continued support in raising funds and awareness; we wouldn’t be here without you. Together, we have raised over $389,000.00!
Conti Family – T-Shirt Sales Duncan Family – Fishing for Ford Gala and Fishing Tournament Facebook Family Fundraisers – In honor and memory of our WS Warriors Flexer Family – Fighting for Flexer Family Bingo Night &
Chocolate Easter Egg Sales McCarthy Construction – Fishing Tournament, Honoring Alex Bieser
We are deeply grateful for your generous donations. Your unwavering kindness and support are fundamental to our mission. Let us honor and remember our beloved Wolfram Warriors, who bravely fought but lost their battle in 2024. Their courage and spirit will forever inspire us and hold a cherished place in our hearts.
Help us Build Awareness & Support Through Rare Disease Day on February 28th. Please help elevate the cause and shine a light on Wolfram syndrome patients and caregivers worldwide. Show your support, start putting together your social media campaigns now, and share the following link and QR Codes to raise money to support WS research projects for 2025.
Research Symposium – June 13th & 14th Paris, France
The 10th International Congress of Clinicians and Researchers focuses on evaluating current research efforts, presenting the results of the TreatWolfram clinical trial, and assessing medical care.
At Bogey Hills Country Club Sponsorships/Tickets Available View Details
2nd Annual Fighting for Flexer Bingo Night
September 27th
For more information email dawnflexer@comcast.net
Fishing For A Cure Gala- November 21st
For Sponsorship Opportunities or Ticket information
contact nsbillard@gmail.com
Thank you to our Sponsors
THANK YOU FOR YOUR CONTINUED SUPPORT
We kindly ask that you consider this opportunity to send a gift today. Your support is invaluable to our efforts as we advocate for the well-being of the Wolfram community and seek a cure.
